β-Phenylethylidenehydrazine [PEH; FIG. 1(1)] is a metabolite of the antidepressant/antipanic/neuroprotective drug phenelzine [PLZ; FIG. 1(2)] and is thought to be formed by the action of monoamine oxidase (MAO) on PLZ.1-4 
PEH shares a number of neurochemical properties with PLZ, including (a) the inhibition of GABA-transaminase (GABA-T) activity;5 (b) the ability to increase brain levels of GABA,5,6 alanine and ornithine;7 and (c) the ability to transiently decrease brain levels of glutamine.5 Inhibition of MAO prior to PLZ administration, prevents some of these effects, such as inhibition of GABA-T, and elevation of GABA and ornithine.8-10 
PEH formation may also contribute to some of the therapeutic effects of PLZ. For example, the anxiolytic properties of PLZ have been shown to be related to the drug's facilitatory effect on GABAergic transmission,11 and given that the increase in GABA appears to be dependent upon PEH formation, it is reasonable to suggest that PEH may mediate the anxiolytic effects of PLZ. Furthermore, PLZ and PEH have been shown to be neuroprotective in animal models of global ischemia,12,13 and while the mechanism(s) for this have not been elucidated, the ability of PLZ to reduce glutamatergic transmission,14,15 the ability of PLZ to sequester reactive aldehydes,12 and the ability of both drugs to increase brain GABA8,16-21 may contribute to neuroprotection. PEH differs from PLZ in that it does not appreciably inhibit MAO activity.5 
Given the strict dietary restrictions that are necessary for individuals taking PLZ due to potentially dangerous interactions between the drug and tyramine-rich foods, PEH may be a useful alternative for conditions thought to involve GABAergic dysfunction and in which PLZ is effective (e.g. depression, social anxiety disorder, panic disorder) but is not used as a first-line drug because of this adverse effect.
There remains a need for improved PEH analogues.
This background information is provided for the purpose of making known information believed by the Applicant to be of possible relevance to the present invention. No admission is necessarily intended, nor should be construed, that any of the preceding information constitutes prior art against the present invention.